Delayed rt-PA Treatment in a Rat Embolic Stroke Model: Diagnosis and Prognosis of Ischemic Injury and Hemorrhagic Transformation with Magnetic Resonance Imaging

Abstract

The authors characterized effects of late recombinant tissue plasminogen activator (rt-PA) administration in a rat embolic stroke model with magnetic resonance imaging (MRI), to assess potential MRI correlates, or predictors, or both, of rt-PA–induced hemorrhage. Diffusion-, perfusion-, and postcontrast T1 -weighted MRI were performed between 4 and 9 hours and at 24 hours after embolic stroke in spontaneously hypertensive rats. Treatment with either rt-PA or saline was started 6 hours after stroke. A spectrophotometric hemoglobin assay quantified hemorrhage severity. Before treatment, relative cerebral blood flow index (rCBFi) and apparent diffusion coefficient (ADC) in the ischemic territory were 30% ± 23% and 60% ± 5% (of contralateral), respectively, which increased to 45% ± 39% and 68% ± 4% 2 hours after rt-PA. After 24 hours, rCBFi and ADC were 27% ± 27% and 59 ± 5%. Hemorrhage volume after 24 hours was significantly greater in rt-PA–treated animals than in controls (8.7 ± 3.7 μL vs. 5.1 ± 2.4 μL, P < 0.05). Before rt-PA administration, clear postcontrast T1 -weighted signal intensity enhancement was evident in areas of subsequent bleeding. These areas had lower rCBFi levels than regions without hemorrhage (23% ± 22% vs. 36% ± 29%, P < 0.05). In conclusion, late thrombolytic therapy does not necessarily lead to successful reperfusion. Hemorrhage emerged in areas with relatively low perfusion levels and early blood–brain barrier damage. Magnetic resonance imaging may be useful for quantifying effects of thrombolytic therapy and predicting risks of hemorrhagic transformation.